Search results for: orphan drug production

Authors: Thorben Kuprat, Julian Becker, Jonas Mayer, Peter Nyhuis

Abstract:

For years now, it has been recognized that logistic performance capability contributes enormously to a production enterprise’s competitiveness and as such is a critical control lever. In doing so, the orientation on customer wishes (e.g. delivery dates) represents a key parameter not only in the value-adding production but also in product regeneration. Since production and regeneration processes have different characteristics, production planning and control measures cannot be directly transferred to regeneration processes. As part of a special research project, the Institute of Production Systems and Logistics Hannover is focused on increasing the logistic performance capability of regeneration processes for complex capital goods. The aim is to ensure logistic targets are met by implementing a model specifically designed to align the capacities and load in regeneration processes.

Keywords: capacity planning, complex capital goods, logistic performance, regeneration process

Procedia PDF Downloads 489

Authors: Jason West

Abstract:

Low profitability in agriculture production along with increasing scrutiny over environmental effects is limiting food production at scale. In contrast, the mining sector offers access to resources including energy, water, transport and chemicals for food production at low marginal cost. Scalable agricultural production can benefit from the nexus of resources (water, energy, transport) offered by mining activity in remote locations. A decision support bioeconomic model for controlled environment vertical farms was used. Four submodels were used: crop structure, nutrient requirements, resource-crop integration, and economic. They escalate to a macro mathematical model. A demonstrable dynamic systems framework is needed to prove productive outcomes are feasible. We demonstrate a generalized bioeconomic macro model for controlled environment production systems in minesites using systems dynamics modeling methodology. Despite the complexity of bioeconomic modelling of resource-agricultural dynamic processes and interactions, the economic potential greater than general economic models would assume. Scalability of production as an input becomes a key success feature.

Keywords: crop production systems, mathematical model, mining, agriculture, dynamic systems

Procedia PDF Downloads 77

Authors: Yi-Ling Chen, Dung-Ying Lin

Abstract:

In the manufacturing process, computer numerical control (CNC) machining plays a crucial role. CNC enables precise machinery control through computer programs, achieving automation in the production process and significantly enhancing production efficiency. However, traditional CNC production lines often require manual intervention for loading and unloading operations, which limits the production line's operational efficiency and production capacity. Additionally, existing CNC automation systems frequently lack sufficient intelligence and fail to achieve optimal configuration efficiency, resulting in the need for substantial time to reconfigure production lines when producing different products, thereby impacting overall production efficiency. Using the NSGA-II algorithm, we generate production line layout configurations that consider field constraints and select robotic arm specifications from an arm list. This allows us to calculate loading and unloading times for each job order, perform demand allocation, and assign processing sequences. The NSGA-II algorithm is further employed to determine the optimal processing sequence, with the aim of minimizing demand completion time and maximizing average machine utilization. These objectives are used to evaluate the performance of each layout, ultimately determining the optimal layout configuration. By employing this method, it enhance the configuration efficiency of CNC production lines and establish an adaptive capability that allows the production line to respond promptly to changes in demand. This will minimize production losses caused by the need to reconfigure the layout, ensuring that the CNC production line can maintain optimal efficiency even when adjustments are required due to fluctuating demands.

Keywords: evolutionary algorithms, multi-objective optimization, pareto optimality, layout optimization, operations sequence

Procedia PDF Downloads 21

Authors: Petra Gajdačová

Abstract:

The presented research deals with a complex evaluation of after-harvest remnants utilization for particleboard production. Agricultural crops that are in the Czech Republic widely grown are in the scope of interest. Researches dealing with composites from agricultural rests solved mostly physical and mechanical properties of produced materials. For the commercialization of these results, however, one another step is essential. It is needed to evaluate the composites production from agricultural rests more comprehensive, take into account all aspects that affect their production, not only material characteristics of produced composites. In this study, descriptive, comparative and synthesis methods were used. Results of this research include a supply stability forecast, technical and technological differences of production of particleboards from agricultural rests and quantification of an economical potential of the agricultural rests.

Keywords: agricultural crops, annual plant, composite material, particleboard

Procedia PDF Downloads 196

Authors: Simona Dostalova, Dita Munzova, Ana Maria Jimenez Jimenez, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

Abstract:

The boom of nanomedicine in recent years has led to the development of numerous new nanomaterials that can be used as nanocarriers in the drug delivery. These nanocarriers can either be synthetic or natural-based. The disadvantage of many synthetic nanocarriers is their toxicity in patient’s body. Protein cages that can naturally be found in human body do not exhibit such disadvantage. However, the release of cargo from some protein cages in target cells can be problematic. As a special type of protein cages can serve the capsid of many viruses, including phage. Phages infect bacterial cells; therefore they are not harmful to human cells. The targeting of phage particles to cancer cells can be solved by producing of empty phage capsids during which the targeting moieties (e.g. peptides) can be cloned into genes of phage capsid to decorate its surface. Moreover, the produced capsids do not contain viral nucleic acid and are therefore not infectious to beneficial bacteria in the patient’s body. The protein cage composed of viral capsid is larger than other frequently used apoferritin cage but its size is still small enough to benefit from passive targeting by Enhanced Permeability and Retention effect. In this work, bacteriophage λ was used, both whole and its empty capsid for delivery of different cytotoxic drugs (cisplatin, carboplatin, oxaliplatin, etoposide and doxorubicin). Large quantities of phage λ were obtained from phage λ-producing strain of E. coli cultivated in medium with 0.2 % maltose. After killing of E. coli with chloroform and its removal by centrifugation, the phage was concentrated by ultracentrifugation at 130 000 g and 4 °C for 3 h. The encapsulation of the drugs was performed by infusion method and four different concentrations of the drugs were encapsulated (200; 100; 50; 25 µg/ml). Free molecules of drugs were removed by dialysis. The encapsulation was verified using spectrophotometric and electrochemical methods. The amount of encapsulated drug linearly increased with the amount of applied drug (determination coefficient R2=0.8013). 76% of applied drug was encapsulated in phage λ particles (concentration of 10 µg/ml), even with the highest applied concentration of drugs, 200 µg/ml. Only 1% of encapsulated drug was detected in phage DNA. Similar results were obtained with encapsulation in phage empty capsid. Therefore, it can be concluded that the encapsulation of drugs into phage particles is efficient and mostly occurs by interaction of drugs with protein capsid.

Keywords: cytostatics, drug delivery, nanocarriers, phage capsid

Procedia PDF Downloads 494

Authors: Mohammadali Abedini Sanigy, Jiangang Fei

Abstract:

In this paper, a mathematical optimization model was developed to maximize the profit in a vegetable production planning problem. It serves as a decision support system that assists farmers in land allocation to crops and harvest scheduling decisions. The developed model can handle different rotation rules in two consecutive cycles of production, which is a common practice in organic production system. Moreover, different production methods of the same crop were considered in the model formulation. The main strength of the model is that it is not restricted to predetermined production periods, which makes the planning more flexible. The model is classified as a mixed integer programming (MIP) model and formulated in PYOMO -a Python package to formulate optimization models- and solved via Gurobi and CPLEX optimizer packages. The model was tested with secondary data from 'Australian vegetable growing farms', and the results were obtained and discussed with the computational test runs. The results show that the model can successfully provide reliable solutions for real size problems.

Keywords: crop rotation, harvesting, mathematical model formulation, vegetable production

Procedia PDF Downloads 189

Authors: Ayşen Melda Çolak, Volkan Okatan, Ercan Yıldız

Abstract:

In our country, fruit production was determined as 17.2 million tons in 2011 according to official data. Turkey fig, apricot, cherry and quince production ranks first in the world. Almost all the regions of our country, despite the growing of fruit 54% of the total fruit production occur in the Mediterranean and the Aegean Region. However, fruit production in the country is consumed in the domestic market and export rates are often very low. In this study, a questionnaire to 100 farmers face-to-face interview. According to the survey, 40% of those in fruit and 7 da of 7 hectares land are small. 30% of soil testing for manufacturers, testing for 20% of the water. Manufacturers who deliberately fertilization rate of only 10%.

Keywords: fruit, generation, potential, Sivasli survey

Procedia PDF Downloads 261

Authors: Shahab Azimi, Siamak Arzanpour, Anahita Sayyar

Abstract:

Asthma and Chronic obstructive pulmonary disease (COPD) are common lung diseases that have a significant global impact. Pressurized metered dose inhalers (pMDIs) are widely used for treatment, but they can have limitations such as high medication release speed resulting in drug deposition in the mouth or oral cavity and difficulty achieving proper synchronization with inhalation by users. Spacers are add-on devices that improve the efficiency of pMDIs by reducing the release speed and providing space for aerosol particle breakup to have finer and medically effective medication. The aim of this study is to optimize the size and cylindrical shape of spacers to enhance their drug delivery performance. The study was based on fluid dynamics theory and employed Ansys software for simulation and optimization. Results showed that optimization of the spacer's geometry greatly influenced its performance and improved drug delivery. This study provides a foundation for future research on enhancing the efficiency of inhalation therapy for lung diseases.

Keywords: asthma, COPD, pressurized metered dose inhalers, spacers, CFD, shape optimization

Procedia PDF Downloads 97

Authors: Yasin I. Tayem, Jamil Ahmed, Mahmood Bahzad, Abdullah Alnama, Fahad Al Asfoor, Mahmood A. Jalil, Mohammed Radhi, Ahmed Alenezi, Khalid A. J. Al-Khaja

Abstract:

Drug-drug interactions (DDIs) represent a significant cause of patient’s morbidity and mortality. The rate of DDIs is rapidly increasing worldwide with the increasing proportion of ageing population and frequent requirement of polypharmacy-prescription of multiple drugs to treat comorbidities. Prescribing physicians are responsible for checking their prescriptions for the presence and severity of DDIs. However, since a large number of new drugs are approved and marketed every year, new interactions between medications are increasingly reported. Consequently, it is no longer practical for physicians to rely only upon their previous knowledge of medicine to avoid potential DDIs. The aim of this study was to explore the perceptions of physicians working at primary healthcare centers in Bahrain towards DDIs and how they manage them during their practice. Methodology: In this cross-sectional study, physicians working at all governmental primary healthcare centers in Bahrain were invited to voluntarily, privately and anonymously respond to a self-administered questionnaire. The questionnaire aims to assess their self-reported knowledge of DDIs and how they check for them in their practice. The participants were requested to provide socio demographic data and information related to their attitudes towards DDIs including strategies they employ for detecting and managing them, and their awareness of drugs which commonly cause DDIs. At the end of the questionnaire, an open-ended item was added to allow participants to further add any comment. Findings and Conclusions: The study is going on currently, and the results and conclusions will be presented at the conference.

Keywords: awareness, drug interactions, health centres, physicians

Procedia PDF Downloads 244

Authors: M. Helen

Abstract:

Chemical graph serves as a convenient model for any real or abstract chemical system. Dendrimers are novel three dimensional hyper branched globular nanopolymeric architectures. Drug delivery scientists are especially enthusiastic about possible utility of dendrimers as drug delivery tool. Dendrimers like poly L lysine (PLL), poly-propylene imine (PPI) and poly-amidoamine (PAMAM), etc., are used as gene carrier in drug delivery system because of their chemical characteristics. These characteristics of chemical compounds are analysed using topological indices (invariants under graph isomorphism) such as Wiener index, Zagreb index, etc., Prof. V. R. Kulli motivated by the application of Zagreb indices in finding the total π energy and derived Gourava indices which is an improved version over Zagreb indices. In this paper, we study the structure of PLL-Dendrimer that has the following applications: reduction in toxicity, colon delivery, and topical delivery. Also, we determine first and second Gourava indices, first and second hyper Gourava indices, product and sum connectivity Gourava indices for PLL-Dendrimer. Gourava Indices have found applications in Quantitative Structure-Property Relationship (QSPR)/ Quantitative Structure-Activity Relationship (QSAR) studies.

Keywords: connectivity Gourava indices, dendrimer, Gourava indices, hyper GouravaG indices

Procedia PDF Downloads 138

Authors: Sariah Abang, S. M. Anisuzzaman, Awang Bono, D. Krishnaiah, S. Rasmih

Abstract:

Biodiesel is a potential renewable energy due to biodegradable and non-toxic. The challenge of its commercialization is associated with high production cost due to its feedstock also useful in various food products. Non-competitive feedstock such as waste cooking oils normally contains a large amount of free fatty acids (FFAs). Large amount of fatty acid degrades the alkaline catalyst in the biodiesel production, thereby decreasing the biodiesel production rate. Generally, biodiesel production processes including esterification and trans-esterification are conducting in a mixed system, in which the hydrodynamic effect on the reaction could not be completely defined. The aim of this study was to investigate the effect of variation rate constant and activation energy on energy consumption of biodiesel production. Usually, the changes of rate constant and activation energy depend on the operating temperature and the degradation of catalyst. By varying the activation energy and kinetic rate constant, the effects can be seen on the energy consumption of biodiesel production. The result showed that the energy consumption of biodiesel is dependent on the changes of rate constant and activation energy. Furthermore, this study was simulated using Aspen HYSYS.

Keywords: methanol, palm oil, simulation, transesterification, triolein

Procedia PDF Downloads 320

Authors: Evy Sulistianingsih, Mariatul Kiftiah, Dedi Rosadi, Heni Wahyuni

Abstract:

This research attempts to analyse palm oil production and rubber production to prosperity of the community of ten districts in West Kalimantan namely Sanggau, Sintang, Sambas, Ketapang, Bengkayang, Landak, Singkawang, Kapuas Hulu, Melawi and Sekadau by panel regression. Gross Domestic Product (GDP) of the districts will be used to be a prosperity indicator on this research. Based on the result of analysis, it can be concluded that palm oil and rubber production statistically give contribution to GDP. Adjusted coefficient determination of Fixed Effect Model indicates that 76% of GDP’s variation can be explained by palm oil and rubber production. In another point of view, there should be a district’s government intervention to regulate the plantations. In addition, there is an obligation of the government to monitor regularly the plantations and to conduct researches in order to govern better planning of lands that have been used to the plantations. So that, the environmental effects that have been caused by the plantation can be diminished.

Keywords: gross domestic product (GDP), panel, palm, welfare

Procedia PDF Downloads 255

Authors: Rajni Kant Panik

Abstract:

The aim of the present study was to develop and evaluate mupirocin loaded nanoparticle incorporated into hydrogel as an infected wound healer. Incorporated Nanoparticle in hydrogel provides a barrier that effectively prevents the contamination of the wound and further progression of infection to deeper tissues. Hydrogel creates moist healing environment on wound space with good fluid absorbance. Nanoparticles were prepared by double emulsion solvent evaporation method using different ratios of PLGA polymer and the hydrogels was developed using sodium alginate and gelatin. Further prepared nanoparticles were then incorporated into the hydrogels. The formulations were characterized by FT-IR and DSC for drug and polymer compatibility and surface morphology was studied by TEM. Nanoparticle hydrogel were evaluated for their size, shape, encapsulation efficiency and for in vitro studies. The FT-IR and DSC confirmed the absence of any drug polymer interaction. The average size of Nanoparticle was found to be in range of 208.21-412.33 nm and shape was found to be spherical. The maximum encapsulation efficiency was found to be 69.03%. The in vitro release profile of Nanoparticle incorporated hydrogel formulation was found to give sustained release of drug. Antimicrobial activity testing confirmed that encapsulated drug preserve its effectiveness. The stability study confirmed that the formulation prepared were stable. Present study complements our finding that mupirocin loaded Nanoparticle incorporated into hydrogel has the potential to be an effective and safe novel addition for the release of mupirocin in sustained manner, which may be a better option for the management of wound. These finding also supports the progression of antibiotic via hydrogel delivery system is a novel topical dosage form for the management of wound.

Keywords: hydrogel, nanoparticle, PLGA, wound healing

Procedia PDF Downloads 311

Authors: Florian Gschösser, Walter Purrer

Abstract:

The paper shows examples for the (environmental) optimization of production processes for asphalt mixtures applied for typical road pavements in Austria and Switzerland. The conducted “from-cradle-to-gate” LCA firstly analyzes the production one cubic meter of asphalt and secondly all material production processes for exemplary highway pavements applied in Austria and Switzerland. It is shown that environmental impacts can be reduced by the application of reclaimed asphalt pavement (RAP) and by the optimization of specific production characteristics, e.g. the reduction of the initial moisture of the mineral aggregate and the reduction of the mixing temperature by the application of low-viscosity and foam bitumen. The results of the LCA study demonstrate reduction potentials per cubic meter asphalt of up to 57 % (Global Warming Potential–GWP) and 77 % (Ozone depletion–ODP). The analysis per square meter of asphalt pavement determined environmental potentials of up to 40 % (GWP) and 56 % (ODP).

Keywords: asphalt mixtures, environmental potentials, life cycle assessment, material production

Procedia PDF Downloads 532

Authors: C. Njoku Paul

Abstract:

This paper deals with systems engineering applications design for offshore oil drilling production platform in the Nigerian Marine Environment. Engineering Design model of the distribution and accumulation of petroleum hydrocarbons discharged into marine environment production platform and sources of impact of an offshore is treated.

Keywords: design of offshore oil drilling production platform, marine, environment, petroleum hydrocarbons

Procedia PDF Downloads 541

Authors: Arpita Roy, Navneeta Bharadvaja

Abstract:

Cancer is an uncontrolled growth of abnormal cells in the body. It is one of the most serious diseases on which extensive research work has been going on all over the world. Structure-based drug designing is a computational approach which helps in the identification of potential leads that can be used for the development of a drug. Plumbagin is a naphthoquinone derivative from Plumbago zeylanica roots and belongs to one of the largest and diverse groups of plant metabolites. Anticancer and antiproliferative activities of plumbagin have been observed in animal models as well as in cell cultures. Plumbagin shows inhibitory effects on multiple cancer-signaling proteins; however, the binding mode and the molecular interactions have not yet been elucidated for most of these protein targets. In this investigation, an attempt to provide structural insights into the binding mode of plumbagin against four cancer receptors using molecular docking was performed. Plumbagin showed minimal energy against targeted cancer receptors, therefore suggested its stability and potential towards different cancers. The least binding energies of plumbagin with COX-2, TACE, and CDK6 are -5.39, -4.93, -and 4.81 kcal/mol, respectively. Comparison studies of plumbagin with different receptors showed that it is a promising compound for cancer treatment. It was also found that plumbagin obeys the Lipinski’s Rule of 5 and computed ADMET properties which showed drug likeliness and improved bioavailability. Since plumbagin is from a natural source, it has reduced side effects, and these results would be useful for cancer treatment.

Keywords: cancer, receptor, plumbagin, docking

Procedia PDF Downloads 143

Authors: Swapnila V. Vanshiv, Hemant P. Joshi, Atul B. Aware

Abstract:

Current study illustrates the formulation of floating microspheres for purpose of gastroretention of Dipyridamole which shows pH dependent solubility, with the highest solubility in acidic pH. The formulation involved hollow microsphere preparation by using solvent evaporation technique. Concentrations of rate controlling polymer, hydrophilic polymer, internal phase ratio, stirring speed were optimized to get desired responses, namely release of Dipyridamole, buoyancy of microspheres, entrapment efficiency of microspheres. In the formulation, the floating microspheres were prepared by using ethyl cellulose as release retardant and HPMC as a low density hydrophilic swellable polymer. Formulated microspheres were evaluated for their physical properties such as particle size and surface morphology by optical microscopy and SEM. Entrapment efficiency, floating behavior and drug release study as well the formulation was evaluated for in vivo gastroretention in rabbits using gamma scintigraphy. Formulation showed 75% drug release up to 10 hr with entrapment efficiency of 91% and 88% buoyancy till 10 hr. Gamma scintigraphic studies revealed that the optimized system was retained in the gastric region (stomach) for a prolonged period i.e. more than 5 hr.

Keywords: Dipyridamole microspheres, gastroretention, HPMC, optimization method

Procedia PDF Downloads 385

Authors: Joanna Kochanska, Dagmara Gornicka, Anna Burduk

Abstract:

The article examines the process of implementing a new assembly line in a manufacturing enterprise of the household appliances industry area. At the initial stages of the project, a decision was made that one of its foundations should be the concept of lean management. Because of that, eliminating as many errors as possible in the first phases of its functioning was emphasized. During the start-up of the line, there were identified and documented all production losses (from serious machine failures, through any unplanned downtime, to micro-stops and quality defects). During 6 weeks (line start-up period), all errors resulting from problems in various areas were analyzed. These areas were, among the others, production, logistics, quality, and organization. The aim of the work was to analyze the occurrence of production failures during the initial phase of starting up the line and to propose a method for determining their critical level during its full functionality. There was examined the repeatability of the production losses in various areas and at different levels at such an early stage of implementation, by using the methods of statistical process control. Based on the Pareto analysis, there were identified the weakest points in order to focus improvement actions on them. The next step was to examine the effectiveness of the actions undertaken to reduce the level of recorded losses. Based on the obtained results, there was proposed a method for determining the critical failures level in the studied areas. The developed coefficient can be used as an alarm in case of imbalance of the production, which is caused by the increased failures level in production and production support processes in the period of the standardized functioning of the line.

Keywords: production failures, level of production losses, new production line implementation, assembly line, statistical process control

Procedia PDF Downloads 128

Authors: Veronika Lesáková, Silvia Slezáková, František Štěpánek

Abstract:

Additive manufacturing technologies producing drug dosage forms aimed at personalized medicine applications are promising strategies with several advantages over the conventional production methods. One of the emerging technologies is 3D printing which reduces manufacturing steps and thus allows a significant drop in expenses. A decrease in material consumption is also a highly impactful benefit as the tested drugs are frequently expensive substances. In addition, 3D printed dosage forms enable increased patient compliance and prevent misdosing as the dosage forms are carefully designed according to the patient’s needs. The incorporation of multiple drugs into a single dosage form further increases the degree of personalization. Our research focuses on the development of 3D printed tablets incorporating multiple drugs (candesartan, losartan) and thermoplastic polymers (e.g., KlucelTM HPC EF). The filaments, an essential feed material for 3D printing,wereproduced via hot-melt extrusion. Subsequently, the extruded filaments of various formulations were 3D printed into tablets using an FDM 3D printer. Then, we have assessed the influence of the internal structure of 3D printed tablets and formulation on dissolution behaviour by obtaining the dissolution profiles of drugs present in the 3D printed tablets. In conclusion, we have developed tablets containing multiple drugs providing modified release profiles. The 3D printing experiments demonstrate the high tunability of 3D printing as each tablet compartment is constructed with a different formulation. Overall, the results suggest that the 3D printing technology is a promising manufacturing approach to dual tablet preparation for personalized medicine.

Keywords: 3D printing, drug delivery, hot-melt extrusion, dissolution kinetics

Procedia PDF Downloads 168

Authors: Norma Binti Alias, Che Rahim Che The, Norfarizan Mohd Said, Sakinah Abdul Hanan, Akhtar Ali

Abstract:

This paper discusses on the transportation of magnetic drug targeting through blood within vessels, tissues and cells. There are three integrated mathematical models to be discussed and analyze the concentration of drug and blood flow through magnetic nanoparticles. The cell therapy brought advancement in the field of nanotechnology to fight against the tumors. The systematic therapeutic effect of Single Cells can reduce the growth of cancer tissue. The process of this nanoscale phenomena system is able to measure and to model, by identifying some parameters and applying fundamental principles of mathematical modeling and simulation. The mathematical modeling of single cell growth depends on three types of cell densities such as proliferative, quiescent and necrotic cells. The aim of this paper is to enhance the simulation of three types of models. The first model represents the transport of drugs by coupled partial differential equations (PDEs) with 3D parabolic type in a cylindrical coordinate system. This model is integrated by Non-Newtonian flow equations, leading to blood liquid flow as the medium for transportation system and the magnetic force on the magnetic nanoparticles. The interaction between the magnetic force on drug with magnetic properties produces induced currents and the applied magnetic field yields forces with tend to move slowly the movement of blood and bring the drug to the cancer cells. The devices of nanoscale allow the drug to discharge the blood vessels and even spread out through the tissue and access to the cancer cells. The second model is the transport of drug nanoparticles from the vascular system to a single cell. The treatment of the vascular system encounters some parameter identification such as magnetic nanoparticle targeted delivery, blood flow, momentum transport, density and viscosity for drug and blood medium, intensity of magnetic fields and the radius of the capillary. Based on two discretization techniques, finite difference method (FDM) and finite element method (FEM), the set of integrated models are transformed into a series of grid points to get a large system of equations. The third model is a single cell density model involving the three sets of first order PDEs equations for proliferating, quiescent and necrotic cells change over time and space in Cartesian coordinate which regulates under different rates of nutrients consumptions. The model presents the proliferative and quiescent cell growth depends on some parameter changes and the necrotic cells emerged as the tumor core. Some numerical schemes for solving the system of equations are compared and analyzed. Simulation and computation of the discretized model are supported by Matlab and C programming languages on a single processing unit. Some numerical results and analysis of the algorithms are presented in terms of informative presentation of tables, multiple graph and multidimensional visualization. As a conclusion, the integrated of three types mathematical modeling and the comparison of numerical performance indicates that the superior tool and analysis for solving the complete set of magnetic drug delivery system which give significant effects on the growth of the targeted cancer cell.

Keywords: mathematical modeling, visualization, PDE models, magnetic nanoparticle drug delivery model, drug release model, single cell effects, avascular tumor growth, numerical analysis

Procedia PDF Downloads 428

Authors: E. P. Doku-Asare, A. Essuman

Abstract:

The materials used for the production of holders are mainly metals and plastic, and these materials are difficult and expensive to process; therefore, the need to explore other materials such as clay for the production of holders. Clay is a viable material for the production of holders due to its plastic nature. Using ceramic materials as a medium for the production of holders does not only serve its purpose but also economically cheaper since the material is mined in Ghana. The study also examines the aesthetic nature of the holders due to the properties found in the material used. Six holders were chosen and were made in a manner that would not take a lot of space. They are Pin holders, Paper holders, Penholders, Paperweight and Umbrella holders. The production technique employed in the execution of this project were the slab method, throwing, and press mold. Results indicated that ceramic holders are durable and long-lasting and can serve the purpose of metallic and plastic holders. The study also found that clay holders are durable due to the fact that clay is from a natural source which ensures permanence and resistance to stress. It is recommended that press molds be used in the production of holders. Clay holders last longer due to the useful properties of clay including very high hardness and strength.

Keywords: ceramics, interior design, Ghana, production technique

Procedia PDF Downloads 166

Authors: Anushka Naidoo, Veron Ramsuran, Maxwell Chirehwa, Paolo Denti, Kogieleum Naidoo, Helen McIlleron, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ngcapu, Nesri Padayatachi

Abstract:

Background: Despite efforts to introduce new drugs and shorter drug regimens for drug-susceptible tuberculosis (TB), the standard first-line treatment has not changed in over 50 years. Rifampicin, isoniazid, and pyrazinamide are critical components of the current standard treatment regimens. Some studies suggest that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic (PK) variability independent of adherence to treatment. Wide between-patient pharmacokinetic variability for rifampin, isoniazid, and pyrazinamide has been reported in prior studies. There may be several reasons for this variability. However, genetic variability in genes coding for drug metabolizing and transporter enzymes have been shown to be a contributing factor for variable tuberculosis drug exposures. Objective: We describe the pharmacokinetics of first-line TB drugs rifampicin, isoniazid, and pyrazinamide and assess the effect of genetic variability in relevant selected drug metabolizing and transporter enzymes on pharmacokinetic parameters of isoniazid and rifampicin. Methods: We conducted the randomized-controlled Improving retreatment success TB trial in Durban, South Africa. The drug regimen included rifampicin, isoniazid, and pyrazinamide. Drug concentrations were measured in plasma, and concentration-time data were analysed using nonlinear-mixed-effects models to quantify the effects of relevant covariates and single nucleotide polymorphisms (SNP’s) of drug metabolizing and transporter genes on rifampicin, isoniazid and pyrazinamide exposure. A total of 25 SNP’s: four NAT2 (used to determine acetylator status), four SLCO1B1, three Pregnane X receptor (NR1), six ABCB1 and eight UGT1A, were selected for analysis in this study. Genotypes were determined for each of the SNP’s using a TaqMan® Genotyping OpenArray™. Results: Among fifty-eight patients studied; 41 (70.7%) were male, 97% black African, 42 (72.4%) HIV co-infected and 40 (95%) on efavirenz-based ART. Median weight, fat-free mass (FFM), and age at baseline were 56.9 kg (interquartile range, IQR: 51.1-65.2), 46.8 kg (IQR: 42.5-50.3) and 37 years (IQR: 31-42), respectively. The pharmacokinetics of rifampicin and pyrazinamide was best described using one-compartment models with first-order absorption and elimination, while for isoniazid two-compartment disposition was used. The median (interquartile range: IQR) AUC (h·mg/L) and Cmax (mg/L) for rifampicin, isoniazid, and pyrazinamide were; 25.62 (23.01-28.53) and 4.85 (4.36-5.40), 10.62 (9.20-12.25) and 2.79 (2.61-2.97), 345.74 (312.03-383.10) and 28.06 (25.01-31.52), respectively. Eighteen percent of patients were classified as rapid acetylators, and 34% and 43% as slow and intermediate acetylators, respectively. Rapid and intermediate acetylator status based on NAT 2 genotype resulted in 2.3 and 1.6 times higher isoniazid clearance than slow acetylators. We found no effects of the SLCO1B1 genotypes on rifampicin pharmacokinetics. Conclusion: Plasma concentrations of rifampicin, isoniazid, and pyrazinamide were low overall in our patients. Isoniazid clearance was high overall and as expected higher in rapid and intermediate acetylators resulting in lower drug exposures. In contrast to reports from previous South African or Ugandan studies, we did not find any effects of the SLCO1B1 or other genotypes tested on rifampicin PK. However, our findings are in keeping with more recent studies from Malawi and India emphasizing the need for geographically diverse and adequately powered studies. The clinical relevance of the low tuberculosis drug concentrations warrants further investigation.

Keywords: rifampicin, isoniazid pharmacokinetics, genetics, NAT2, SLCO1B1, tuberculosis

Procedia PDF Downloads 187

Authors: Saurabh B. Ganorkar, Atul A. Shirkhedkar

Abstract:

The need for investigations protecting against toxic impurities though seems to be a primary requirement; the impurities which may prove non - toxic can be explored for their therapeutic potential if any to assist advanced drug discovery. The essential role of pharmaceutical analysis can thus be extended effectively to achieve it. The present study successfully achieved these objectives with characterization of major degradation products as impurities for Zileuton which has been used for to treat asthma since years. The forced degradation studies were performed to identify the potential degradation products using Ultra-fine Liquid-chromatography. Liquid-chromatography-Mass spectrometry (Time of Flight) and Proton Nuclear Magnetic Resonance Studies were utilized effectively to characterize the drug along with five major oxidative and hydrolytic degradation products (DP’s). The mass fragments were identified for Zileuton and path for the degradation was investigated. The characterized DP’s were subjected to In-Silico studies as XP Molecular Docking to compare the gain or loss in binding affinity with 5-Lipooxygenase enzyme. One of the impurity of was found to have the binding affinity more than the drug itself indicating for its potential to be more bioactive as better Antiasthmatic. The close structural resemblance has the ability to potentiate or reduce bioactivity and or toxicity. The chances of being active biologically at other sites cannot be denied and the same is achieved to some extent by predictions for probability of being active with Prediction of Activity Spectrum for Substances (PASS) The impurities found to be bio-active as Antineoplastic, Antiallergic, and inhibitors of Complement Factor D. The toxicological abilities as Ames-Mutagenicity, Carcinogenicity, Developmental Toxicity and Skin Irritancy were evaluated using Toxicity Prediction by Komputer Assisted Technology (TOPKAT). Two of the impurities were found to be non-toxic as compared to original drug Zileuton. As the drugs are purposed and repurposed effectively the impurities can also be; as they can have more binding affinity; less toxicity and better ability to be bio-active at other biological targets.

Keywords: UFLC, LC-MS-TOF, NMR, Zileuton, impurities, toxicity, bio-activity

Procedia PDF Downloads 195

Authors: Yogeeta O. Agrawal, Hitendra S. Mahajan, Sanjay J. Surana

Abstract:

Methotrexate is effective in controlling recalcitrant psoriasis when administered by the oral or parenteral route long-term. However, the systematic use of this drug may provoke any of a number of side effects, notably hepatotoxic effects. To reduce these effects, clinical studies have been done with topical MTx. It is useful in treating a number of cutaneous conditions, including psoriasis. A major problem in topical administration of MTx currently available in market is that the drug is hydrosoluble and is mostly in the dissociated form at physiological pH. Its capacity for passive diffusion is thus limited. Localization of MTx in effected layers of skin is likely to improve the role of topical dosage form of the drug as a supplementary to oral therapy for treatment of psoriasis. One of the possibilities for increasing the penetration of drugs through the skin is the use of Nanostructured lipid Carriers. The objective of the present study was to formulate and characterize Methotrexate loaded Nanostructured Lipid Carriers (MtxNLCs), to understand in vitro drug release and evaluate the role of the developed gel in the topical treatment of psoriasis. MtxNLCs were prepared by solvent diffusion technique using 3(2) full factorial design.The mean diameter and surface morphology of MtxNLC was evaluated. MtxNLCs were lyophilized and crystallinity of NLC was characterized by Differential Scanning Calorimtery (DSC) and powder X-Ray Diffraction (XRD). The NLCs were incorporated in 1% w/w Carbopol 934 P gel base and in vitro skin deposition studies in Human Cadaver Skin were conducted. The optimized MtxNLCs were spherical in shape, with average particle size of 253(±9.92)nm, zeta potential of -30.4 (±0.86) mV and EE of 53.12(±1.54)%. DSC and XRD data confirmed the formation of NLCs. Significantly higher deposition of Methotrexate was found in human cadaver skin from MtxNLC gel (71.52 ±1.23%) as compared to Mtx plain gel (54.28±1.02%). Findings of the studies suggest that there is significant improvement in therapeutic index in treatment of psoriasis by MTx-NLCs incorporated gel base developed in this investigation over plain drug gel currently available in the market.

Keywords: methotrexate, psoriasis, NLCs, hepatotoxic effects

Procedia PDF Downloads 430

Authors: Khelfaoui Rachid, Chekifi Tawfiq, Dennai Brahim, Maazouzi A. Hak

Abstract:

A numerical and experimental studies of passive micro drops production have been presented. This paper focuses on the modeling of micro-oscillators systems which are composed by passive amplifier without moving part. The micro-system modeling is based on geometrical oscillators form. An asymmetric micro-oscillator design that is based on a bistable fluidic amplifier is proposed. The characteristic size of the channels is generally about 35 microns of depth. The numerical results indicate that the production and manipulation of microdrops are possible with passive device within a typical oscillators chamber of 2.25 mm diameter and 0.20 mm length when the Reynolds number is Re = 490. The novel micro drops method that is presented in this study provides a simple solution about the production of microdrops problems in micro system. We undertake an experimental step. The first part is based on the realisation of sample oscillator; the second part is consisted of visualization, production and manipulation of microdrops.

Keywords: modelling, miscible, micro drops, production, oscillator sample, capillary

Procedia PDF Downloads 378

Authors: Mandy Wilson, Emma Vieira, Jocelyn Jones, Alice V. Brown, Lindey Andrews, Louise Southalan, Jackie Oakley, Dorothy Bagshaw, Patrick Egan, Laura Dent, Duc Dau, Lucy Spanswick

Abstract:

Alcohol and drug dependency are pertinent issues for those experiencing homelessness. This includes Aboriginal and Torres Strait Islander people, Australia’s traditional owners, living in Perth, Western Australia (WA). Societal narratives around the drivers behind drug and alcohol dependency in Aboriginal communities, particularly those experiencing homelessness, have been biased and unchanging, with little regard for complexity. This can include the idea that Aboriginal people have ‘chosen’ to use alcohol or other drugs without consideration for intergenerational trauma and the trauma of homelessness that may influence their choices. These narratives have flow-on impacts on policies and services that directly impact Aboriginal people experiencing homelessness. In 2021, we commenced a project which aimed to listen to and elevate the voices of 70-90 Aboriginal people experiencing homelessness in Perth. The project is community-driven, led by an Aboriginal Community Controlled Organisation in partnership with a university research institute. A community-ownership group of Aboriginal Elders endorsed the project’s methods, chosen to ensure their suitability for the Aboriginal community. In this paper, we detail these methods, including semi-structured interviews influenced by an Aboriginal yarning approach – an important style of conversation for Aboriginal people which follows cultural protocols; and photovoice – supporting people to share their stories through photography. Through these engagements, we detail the reasons Aboriginal people in Perth shared for using alcohol or other drugs while experiencing homelessness. These included supporting their survival on the streets, managing their mental health, and coping while on the journey to finding support. We also detail why they sought to discontinue alcohol and other drug use, including wanting to reconnect with family and changing priorities. Finally, we share how Aboriginal people experiencing homelessness have said they are impacted by their family’s alcohol and other drug use, including feeling uncomfortable living with a family who is drug and alcohol-dependent and having to care for grandchildren despite their own homelessness. These findings provide a richer understanding of alcohol and drug use for Aboriginal people experiencing homelessness in Perth, shedding light on potential changes to targeted policy and service approaches.

Keywords: Aboriginal and Torres Strait Islander peoples, alcohol and other drugs, homelessness, community-led research

Procedia PDF Downloads 131

Authors: M. Cizmesija, N. Erjavec, V. Bahovec

Abstract:

While the European Union (EU) harmonized methodology is a benchmark of worldwide used business survey (BS) methodology, the choice of variables that are components of the confidence indicators, as the leading indicators, is not strictly determined and unique. Therefore, the aim of this paper is to investigate and to quantify the relationship between all business survey variables in manufacturing industry and industrial production as a reference macroeconomic series in Croatia. The assumption is that there are variables in the business survey, that are not components of Industrial Confidence Indicator (ICI) and which can accurately (and sometimes better then ICI) predict changes in Croatian industrial production. Empirical analyses are conducted using quarterly data of BS variables in manufacturing industry and Croatian industrial production over the period from the first quarter 2005 to the first quarter 2013. Research results confirmed the assumption: three BS variables which is not components of ICI (competitive position, demand and liquidity) are the best leading indicator then ICI, in forecasting changes in Croatian industrial production instantaneously, with one, two or three quarter ahead.

Keywords: balance, business survey, confidence indicators, industrial production, forecasting

Procedia PDF Downloads 474

Authors: Marlies Achenbach

Abstract:

System competencies play a key role to ensure an effective and efficient improvement of production systems. Thus, there can be observed an increasing demand for developing system competencies in industry as well as in engineering education. System competencies consist of the following two main abilities: Evaluating the current state of a production system and developing a target state. The innovative course ‘multi-perspective learning in a real production plant (multi real)’ is developed to create a learning setting that supports the development of these system competencies. Therefore, the setting combines two innovative aspects: First, the Learning takes place in heterogeneous groups formed by students as well as professionals and managers from industry. Second, the learning takes place in a real production plant. This paper presents the innovative didactic concept of ‘multi real’ in detail, which will initially be implemented in October/November 2016 in the industrial engineering, logistics and mechanical master’s program at TU Dortmund University.

Keywords: experiential learning, heterogeneous groups, improving production systems, system competencies

Procedia PDF Downloads 426

Authors: Abdulaziz Alakeel, Roaa Alamri, Abdulrahman Alomair, Mohammed Fouda

Abstract:

Introduction: Ibrutinib is a selective, potent, and irreversible small-molecule inhibitor of Bruton's tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue (CYS-481) at the active site of Btk, leading to inhibition of Btk enzymatic activity. The drug is indicated to treat certain type of cancers such as mantle cell lymphoma (MCL), chronic lymphocytic leukaemia and Waldenström's macroglobulinaemia (WM). Cardiac failure is a condition referred to inability of heart muscle to pump adequate blood to human body organs. There are multiple types of cardiac failure including left and right-sided heart failure, systolic and diastolic heart failures. The aim of this review is to evaluate the risk of cardiac failure associated with the use of ibrutinib and to suggest regulatory recommendations if required. Methodology: Signal Detection team at the National Pharmacovigilance Center (NPC) of Saudi Food and Drug Authority (SFDA) performed a comprehensive signal review using its national database as well as the World Health Organization (WHO) database (VigiBase), to retrieve related information for assessing the causality between cardiac failure and ibrutinib. We used the WHO- Uppsala Monitoring Centre (UMC) criteria as standard for assessing the causality of the reported cases. Results: Case Review: The number of resulted cases for the combined drug/adverse drug reaction are 212 global ICSRs as of July 2020. The reviewers have selected and assessed the causality for the well-documented ICSRs with completeness scores of 0.9 and above (35 ICSRs); the value 1.0 presents the highest score for best-written ICSRs. Among the reviewed cases, more than half of them provides supportive association (four probable and 15 possible cases). Data Mining: The disproportionality of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by WHO-UMC to measure the reporting ratio. Positive IC reflects higher statistical association while negative values indicates less statistical association, considering the null value equal to zero. The results of (IC=1.5) revealed a positive statistical association for the drug/ADR combination, which means “Ibrutinib” with “Cardiac Failure” have been observed more than expected when compared to other medications available in WHO database. Conclusion: Health regulators and health care professionals must be aware for the potential risk of cardiac failure associated with ibrutinib and the monitoring of any signs or symptoms in treated patients is essential. The weighted cumulative evidences identified from causality assessment of the reported cases and data mining are sufficient to support a causal association between ibrutinib and cardiac failure.

Keywords: cardiac failure, drug safety, ibrutinib, pharmacovigilance, signal detection

Procedia PDF Downloads 129

Authors: Jillian M. Hagel, Joseph E. Tucker, Peter J. Facchini

Abstract:

With the aim of establishing a holistic approach for the treatment of central nervous system (CNS) disorders, we are pursuing a drug development program rapidly progressing through discovery and characterization phases. The drug candidates identified in this program are referred to as neuroplastogens owing to their ability to mediate neuroplasticity, which can be beneficial to patients suffering from anxiety, depression, or posttraumatic stress disorder. These and other related neuropsychiatric conditions are associated with the onset of neuronal atrophy, which is defined as a reduction in the number and/or productivity of neurons. The stimulation of neuroplasticity results in an increase in the connectivity between neurons and promotes the restoration of healthy brain function. We have synthesized a substantial catalogue of proprietary indolethylamine derivatives based on the general structures of serotonin (5-hydroxytryptamine) and psychedelic molecules such as N,N-dimethyltryptamine (DMT) and psilocin (4-hydroxy-DMT) that function as neuroplastogens. A primary objective in our screening protocol is the identification of derivatives associated with a significant reduction in hallucination, which will allow administration of the drug at a dose that induces neuroplasticity and triggers other efficacious outcomes in the treatment of targeted CNS disorders but which does not cause a psychedelic response in the patient. Both neuroplasticity and hallucination are associated with engagement of the 5HT2A receptor, requiring drug candidates differentially coupled to these two outcomes at a molecular level. We use novel and proprietary artificial intelligence algorithms to predict the mode of binding to the 5HT2A receptor, which has been shown to correlate with the hallucinogenic response. Hallucination is tested using the mouse head-twitch response model, whereas mouse marble-burying and sucrose preference assays are used to evaluate anxiolytic and anti-depressive potential. Neuroplasticity is assays using dendritic outgrowth assays and cell-based ELISA analysis. Pharmacokinetics and additional receptor-binding analyses also contribute the selection of lead candidates. A summary of the program is presented.

Keywords: neuroplastogen, non-hallucinogenic, drug development, anxiety, depression, PTSD, indolethylamine derivatives, psychedelic-inspired, 5-HT2A receptor, computational chemistry, head-twitch response behavioural model, neurite outgrowth assay

Procedia PDF Downloads 138